Rothia in Nonsmall Cell Lung Cancer is Associated With Worse Survival.

INTRODUCTION: The microbiome is known to play a significant role in cancer biology; however, few studies have elucidated its relationship with Nonsmall Cell Lung Cancer (NSCLC) patient outcomes. We hypothesized that there are specific microorganisms that are closely related with NSCLC patient survival. METHODS: Total of 647 NSCLC (Adenocarcinoma and Squamous Cell Carcinoma combined) patients in The Cancer Genome Atlas (TCGA) were analyzed using the R software. RESULTS: A Volcano Plot was analyzed with the patients divided into Short and Long Survivors by overall survival of 0.9 years, and we found that a bacterium Rothia was significantly abundant in Short Survivors, and Blastococcus, Leptospira, and Haematobacter in Long Survivors, but presence of Rothia alone was associated with overall survival. The age, race, subtype, and sex were not significantly different by the presence of Rothia in NSCLC. Unexpectedly, Rothia-positive NSCLC was associated with less cell proliferation by gene set enrichment analysis, Mki67 expression, proliferation score, with less fraction altered and homologous recombination deficiency, and with high infiltration of stromal cells, indicating favorable oncological characteristics. Further, Rothia-positive tumors were associated with significantly higher infiltration of CD8 T cells, CD4 T cells, Monocytes, and NK cells, and high interferon-gamma response, T-cell receptor richness, cytolytic activity, indicating favorable tumor immune microenvironment. CONCLUSIONS: NSCLC with Rothia was associated with worse survival but also with favorable oncological characteristics such as less cell proliferation and favorable tumor immune microenvironment. We cannot help but speculate that Rothia in NSCLC is associated with mortality unrelated to oncological characteristics.

Approach to Resectable N1 Non-Small Cell Lung Cancer: An Analysis of the National Cancer Database.

BACKGROUND: In patients with clinical N1 disease, minimally invasive surgery (MIS) has potentially better perioperative outcome compared to open thoracotomy. Additionally, whether adjuvant or neoadjuvant chemotherapy produces the best long-term survival is still debatable. METHODS: We queried The National Cancer Database for patients with clinical N1 NSCLC who underwent surgical resection between 2010 and 2014. Comparison between patients receiving MIS and patients who underwent open thoracotomy was done using an intention-to-treat analysis. Comparison was also done among neoadjuvant, adjuvant chemotherapy, and only surgery. Proportional hazard models were used to evaluate the effects of surgical approach and timing of chemotherapy on overall survival. RESULTS: A total of 1440 and 3942 patients underwent MIS and open thoracotomy respectively. MIS achieved better surgical margins (90.0% versus 88.6%) and shorter length of stay (6.5 ± 6.5 versus 7.3 ± 6.4 d, P ≤ 0.01) compared to open thoracotomy. There were no differences in 30-day and 90-day mortality, nor readmission rates. Neoadjuvant and adjuvant chemotherapy were administered to 13.5% and 57.2% of patients respectively. There was no significant difference in the 5-year overall survival between MIS and open thoracotomy (46% versus 46% P = 0.08). There was significantly better 5-year overall survival in neoadjuvant and adjuvant chemotherapy versus only surgery, but no difference between neoadjuvant and adjuvant chemotherapy (48% versus 47% versus 44%, P < 0.01). CONCLUSIONS: In clinical N1 NSCLC, MIS does not compromise oncological quality or overall survival when compared to open thoracotomy. Overall survival improved in patients treated with chemotherapy but there is no difference when given as neoadjuvant versus adjuvant chemotherapy.

Carcinogen-induced squamous papillomas and oncogenic progression in the absence of the SSeCKS/AKAP12 metastasis suppressor correlate with FAK upregulation.

The ability of SSeCKS/Gravin/AKAP12 (SSeCKS) to negatively regulate cell cycle progression is thought to relate to its spatiotemporal scaffolding activity for key signaling molecules such as protein kinase A and C, calmodulin and cyclins. SSeCKS is downregulated upon progression to malignancy in many cancer types, including melanoma and nonmelanoma skin cancer. The forced re-expression of SSeCKS is especially potent in suppressing metastasis through the inhibition of VEGF-mediated neovascularization. We have previously shown that SSeCKS-null (KO) mice exhibit hyperplasia and focal dysplasia in the prostate marked by activated Akt. To address whether KO mice exhibit increased skin carcinogenesis, WT and KO C57BL/6 mice were treated topically with 12-O-tetradecanoylphorbol-13-acetate and 7,12-dimethylbenzanthracene. Compared to WT mice, KO mice developed squamous papillomas more rapidly and in greater numbers and also exhibited significantly increased progression to squamous cell carcinoma. Untreated KO epidermal layers were thicker than those in age-matched WT mice and exhibited significantly increased levels of FAK and phospho-ERK1/2, known mediators of carcinogen-induced squamous papilloma progression to carcinoma. Compared to protein levels in WT mouse embryo fibroblasts (MEF), SSeCKS levels were increased in FAK-null cells, whereas FAK levels were increased in SSeCKS-null cells. RNAi studies in WT MEF cells suggest that SSeCKS and FAK attenuate each other's expression. Our study implicates a role for SSeCKS in preventing of skin cancer progression possibly through negatively regulating FAK expression.